fgfr3在pth134促骨合成代谢中的作用及机制分析word格式论文.docxVIP

体内间断给予 PTH1-34 处理的情况下，FGFR3 敲除小鼠骨皮质 BMD 和厚度的增加幅度较 WT 小鼠更明显，但其骨小梁 BV/TV 以及 BMD 增加幅度与野生型相比没有显著 差别。FGFR3 敲除小鼠骨组织中成骨细胞和破骨细胞分化标志基因在 PTH1-34 处理后 的增加幅度均较野生型明显。我们的研究结果提示：抑制 FGFR3 的表达可能有助于增 强 PTH 的促骨合成作用，这为临床上 PTH 联合用药治疗骨质疏松提供了新的策略。关键词：PTH，FGFR3，成骨细胞，骨重建，骨形成The role of FGFR3 in anabolic effect of PTH1-34 on boneAbstractSkeleton is the largest organ in the body, three major functions of which are supporting body, locomotion, and protection of internal organs. In addition, bone is the main regulator of mineral homestasis including calcium, phosphate and magnesium. Bone is a dynamic organ with continous remodeling that maintains bone strength and integrity. Bone remodling, which involves resorption of bone mediated by osteoclasts and formation of new bone mediated by osteoblasts, is a dynamic equilibrium. Disturbance of this process will lead to bone metabolism disorders. For example, when bone resorption overwhelms bone formation, osteoporosis will subsequently occur. Osteoporosis is a skeletal disorder characterized by low bone mass, disruption of microarchitecture and increased bone fragility, all of which leads to increased risk of bone fracture. Now, along with the aging of population, osteoporosis is already a global healthy problem adversely influencing the life quality of old people.Currentlly, drugs used to treat osteoporosis mainly by inhibiting bone resorption (such as estrogen of calcitonin and bisphosphonates, etc) and by promoting bone formation (such as PTH, etc), or by simultaneously targeting bone resorption and formation (such as traditional Chinese medicine, strontium ranelate, etc). Although anti-resorption drugs could efficiently prevent bone loss and can increase BMD by up to 10%, low bone turnover rate may cause accumulation of bone fatigue and resulatant increase of fracture risk. So far, parathyroid hormone 1-34 (PTH1-34) is the only bone anabolic drug approved by FDA to treat osteoporosis, which directly stimulates bone formation by increasing osteobal